What is the role of Progesterone (a steroid hormone)?

From the Guidelines

Progesterone should be prescribed as natural micronized progesterone (MP) for hormonal replacement therapy in adolescents and young women with chemo- or radio-induced premature ovarian insufficiency, due to its favorable profile in minimizing hormonal-related cardiovascular risks and having a neutral or beneficial effect on blood pressure 1.

Key Points

• Progesterone plays a crucial role in female reproductive health, including preparing the uterine lining for potential pregnancy and maintaining pregnancy by supporting the endometrium.
• Natural micronized progesterone (MP) is recommended due to its safer pharmacological profile compared to synthetic progestogens, with a lower risk of cardiovascular events and thrombotic risk 1.
• The European Society for Human Reproduction and Embryology (ESHRE) includes MP among the recommended progestogens in HRT in adult women with ovarian insufficiency 1.
• Other progestins, such as medroxyprogesterone acetate (MPA), dydrogesterone, and norethisterone acetate (NA), may also be used, but their safety profiles and effectiveness may vary 1.
• In the context of preterm birth prevention, vaginal progesterone has been shown to reduce the risk of preterm birth in women with a short cervix, particularly those with a cervical length of 25 mm or less 1.

Forms and Dosage

• Progesterone is available as a medication in various forms, including oral capsules (typically 100-200mg daily), vaginal suppositories or gels (90-100mg daily), and intramuscular injections (50-100mg) 1.
• The most studied formulations of vaginal progesterone for the treatment of a short cervix are 90-mg (8%) progesterone gel and 200-mg micronized progesterone capsules 1.

Clinical Considerations

• Clinicians should choose between a sequential and continuous regimen of administration, with the latter preventing withdrawal bleeding 1.
• The dose of progestogen is based on the concurrent dose of estrogen administered 1.
• Patient counseling is necessary when prescribing vaginal progesterone for the indication of a short cervix, as its use is currently off-label 1.

From the FDA Drug Label

PATIENT INFORMATION Progesterone Capsules, 100 mg and 200 mg Rx only What is progesterone capsules Progesterone capsules contain the female hormone called progesterone. What is progesterone capsules used for? Treatment of Menstrual Irregularities Progesterone capsules are used for the treatment of secondary amenorrhea (absence of menstrual periods in women who have previously had a menstrual period) due to a decrease in progesterone Protection of the Endometrium (Lining of the Uterus) Progesterone capsules are used in combination with estrogen-containing medications in a postmenopausal woman with a uterus (womb).

Progesterone is used for the treatment of menstrual irregularities and to protect the endometrium in postmenopausal women with a uterus. The main uses of progesterone capsules are:

• Treatment of secondary amenorrhea due to a decrease in progesterone
• Protection of the endometrium in combination with estrogen-containing medications in postmenopausal women with a uterus 2

From the Research

Progesterone Uses

• Progesterone is used to prevent preterm birth in women with a history of spontaneous preterm birth and/or sonographic short cervix 3
• It is also used to support early pregnancy in women with recurrent miscarriage, as it has immunomodulatory effects and plays a critical role in the expression of various growth factors and cytokines 4
• Progesterone has a significant role in maintaining early and successful pregnancy to term, and evidence-based strategies using progesterone can help reduce miscarriage rates and improve assisted reproductive technology (ART) outcomes 5

Progesterone Efficacy

• Progesterone supplementation has been shown to reduce the rate of miscarriage in women with threatened miscarriage, with a relative risk of 0.70 (95% CI 0.52,0.94) compared to placebo or no treatment 6
• However, progesterone supplementation did not significantly improve the incidence of preterm and live birth in women with threatened miscarriage 6
• The efficacy of combined oestrogen and progesterone therapy for preventing miscarriage is uncertain, with insufficient evidence from randomized controlled trials to support its use 7

Progesterone Recommendations

• Women at high risk of preterm birth should be offered daily vaginal progesterone or weekly 17-OHPC treatment to prevent preterm birth, with the preparation used decided by the woman and her clinician 3
• Progesterone therapy is not recommended for the prevention of preterm birth in asymptomatic women with no prior history of previous preterm birth, no mid-trimester loss, or no short cervical length 3
• Further research is needed to determine the efficacy of progestogen treatment in women with recurrent miscarriage and to assess the use of combined oestrogen and progesterone for preventing miscarriages 4, 7